Hydroxystyrenes, such as p-hydroxystyrene (pHS; also known as p-vinylphenol) and acetylated derivatives thereof, such as p-acetoxystyrene (pAS), are aromatic compounds that have potential utility in a wide variety of industrial applications. For example, these compounds have applications as monomers for the production of resins, elastomers, adhesives, coatings, automotive finishes, inks and photoresists, as well as in electronic materials. They may also be used as additives in elastomer and resin formulations.
A number of methods for the chemical synthesis of hydroxystyrenes and acetylated derivatives thereof are known. However, these methods generally require expensive reagents, harsh conditions, and give relatively low yields. Examples of starting reagents used in the chemical synthesis of pHS include p-hydroxycinnamic acid (pHCA; Sovish J. Org. Chem. 24:1345-1347 (1959); U.S. Pat. No. 5,274,060), p-hydroxybenzaldehyde (U.S. Pat. No. 4,316,995), ortho or para-hydroxyarylcarboxylic acids (Australian Patent Application No. 7247129), caffeic acid (U.S. Pat. No. 5,324,804), trans-3,5-di-tert-butyl-4-hydroxycinnamic acid (Munteanu et al. J. Thermal Anal. 37:411-426 (1991)), and p-alpha-amino-ethylphenol (U.S. Pat. No. 5,493,062), and hydroxybenzaldehydes and malonic acid (Simpson et al., Tetraheron Lett. 46: 6893 (2005)).
Tyrosine, (S)-2-amino-3-(4-hydroxy-phenyl)propanoic acid, provides a readily available and relatively low cost reagent which has potential of being a reagent for producing pHS. Tyrosine was used as the starting reagent in the synthesis of (S)4-(2-chloro-3-(4-n-dodecyloxy)phenylpropionato)-4′4(2-methyl)butyloxy-biphenylcarboxylate (CDPMBB) in Kumar and Pisipati (Z. Naturforsch. 57a:803-806 (2002)). The initial reaction was diazochlorination of tyrosine by nucleophilic substitution in the presence of sodium nitrite to form (S)-2-chloro-3-(4-hydroxy)phenyl propionic acid. Yields of the reaction were poor, and by-products resulting from nitration or chlorination of the aromatic ring made purification difficult.
Side chain protected tyrosine, tyrosine t-butyl ether, was brominated in the presence of HBr, KBr, and sodium nitrite (Souers et al., Synthesis 4:583-585 (1999)). The presence of the protecting group on the phenol moiety complicates the use of this product as a reagent for producing pHS.
There is a need for a method for the chemical synthesis of pHS from tyrosine which is simple and efficient, that produces product in high yield and avoids the complications of by products generated from the use of a side chain protected tyrosine. Applicants have solved the stated problem by the discovery of a two step reaction for the conversion of tyrosine to brominated tyrosine intermediates coupled with their subsequent conversion to p-hydroxstyrene under basic conditions.